Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy

Thitima Pewklang; Kantapat Chansaenpak; Siti Nursyahirah Bakar; Rung-Yi Lai; Chin Siang Kue; Anyanee Kamkaew

doi:10.3389/fchem.2022.1015883

Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy

Front Chem. 2022 Nov 2:10:1015883. doi: 10.3389/fchem.2022.1015883. eCollection 2022.

Authors

Thitima Pewklang¹, Kantapat Chansaenpak², Siti Nursyahirah Bakar³, Rung-Yi Lai¹, Chin Siang Kue³, Anyanee Kamkaew¹

Affiliations

¹ School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
² National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani, Thailand.
³ Faculty of Health and Life Sciences, Management and Science University, Shah Alam, Selangor, Malaysia.

Abstract

Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX₂ was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX₂ showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX₂ by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX₂ could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX₂ can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.

Keywords: PDT; acetazolamide; aza-BODIPY; carbonic anhydrase IX (CA9); hypoxia.